Moving Towards the Delivery of Outpatient T-Cell Engaging Therapy for the Management of Multiple Myeloma

Bispecific antibodies (BsAbs) and chimeric antigen receptor T-cells (CAR-T) are T-cell engagers (TCEs) becoming increasingly important for treatment of multiple myeloma. The purpose of this paper is to review TCE side effects and their management. In doing so, we will demonstrate that outpatient delivery of TCEs can be safe and advantageous for patients and healthcare systems. The initial introduction of TCE therapy has been limited to the inpatient setting due to risk of cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS). These complications, which typically occur in the first few weeks of initiating therapy, are mediated by an exaggerated inflammatory response triggered by TCE binding to tumor cells. BsAb trials have demonstrated a high overall incidence of CRS, though severe cases are rare as is development of ICANS. The incidence and severity of CRS and ICANS seem to be higher with CAR-T therapy. Predictors of development and severity of CRS and ICANS include disease bulk, lymphodepletion strategy, CAR-T construct used, and pattern of expression of the tumor antigen. Prevention strategies include step-up dosing, disease bulk reduction, prophylactic steroid use and premedication. Treatment strategies include the use of steroids and cytokine binders/blockers, such as anti-IL6 and anti-IL1 agents. Effective prophylaxis and management of CRS and ICANS has reduced the impact of these complications and opened the potential for outpatient delivery. Outpatient delivery of TCEs is possible with appropriate preventative strategies, education, and established pathways for prompt transition to inpatient management if needed.